We have recently demonstrated that short-term exposure to PM2.5 results in elevation of blood pressure (BP) in humans and in an animal model. This pro-hypertensive response may be a key mechanism linking PM2.5 to an increase in both short and long-term cardiovascular risk and therefore merits further detailed investigation. We hypothesize that PM2.5 mediated hypertension results from ROS mediated reduction in nitric oxide (*NO) bioavailability and up-regulation of endogenous vasoconstrictor mechanisms. We propose to test this hypothesis in predisposed animal models (where ROS is the predominant basis of hypertension) as well as in humans who have been exposed to air pollution through a series of studies involving a broad interdisciplinary group. In the first specific aim, we will perform studies on C57BI/6 mice that have been exposed to PM2 5 or filtered air (FA) for 8 weeks followed by infusion of angiotensin II (A-ll) or placebo. The effect of PM2.5 on BP, ROS pathways, vascular reactivity and a factor analysis of PM2.5 components most responsible for these effects will be evaluated. In the second specific aim, we will investigate the role of vasoconstrictor pathways activated by ROS in response to PM2.5. In the third specific aim we will assess the impact of strategies that antagonize pathways responsible for heightened ROS production. If our hypothesis is correct, abrogation of ROS generation will improve PM2 5 mediated effects on the vasculature and hypertension. These experiments will provide the basis for the human study where we postulate that BP is significantly modulated by immediate (hours) and short-term (days) alterations in ambient PM2.5 exposure in Detroit and New York City and that increases in BP on exposure to PM2 5 occurs through ROS mediated pathway(s). The effect of ambient air pollution on BP and oxidative stress in humans will be tested. If our hypothesis is correct, then treatment with an antioxidant will significantly blunt or eliminate the relationship between BP and PM2.5 mass. By testing this hypothesized mechanism in detailed animal studies in conjunction with the subsequent corroboration in humans, this proposal offers an unprecedented opportunity to elucidate the physiologically relevant mechanisms responsible for the pro-hypertensive actions of PM2.5 exposure. These insights may lead to future testable methods potentially capable of reducing the tremendous public health burden of PM2.5.